POS0740 IMPACT OF TIME TO REMISSION, FLARES AND EXPOSURE TO IMMUNOSUPPRESSIVES ON THE DEVELOPMENT OF ADVANCED CHRONIC KIDNEY DISEASE (STAGE IV OR WORSE) IN LUPUS NEPHRITIS
Authors: K. Tselios, D. D. Gladman, J. Su, M. B. Urowitz
Journal: Annals of the Rheumatic Diseases (2022)

Background Lupus nephritis (LN) affects up to 40% of patients with SLE and leads to end stage kidney disease (ESKD) in 17-33% after 10 years. The prevalence of chronic kidney disease stage IV (estimated glomerular filtration rate, eGFR=15-29ml/min/1.73m 2 ) is not known; however, approximately two thirds of such patients will progress to ESKD after 6 years on average. 1 Objectives To determine the impact of time to remission and flares on the development of advanced CKD (stage IV or worse) in LN. Methods Patients with LN based on biopsy or abnormal proteinuria (&gt;0.5g/day) with or without hematuria/pyuria/casts for two consecutive visits in the absence of other plausible explanation were retrieved from the Toronto Lupus Clinic database. Individuals with advanced CKD at baseline were excluded. All patients were followed for at least 5 years. The primary outcome was the development of advanced CKD (eGFR≦29ml/min/1.73m 2 ). Remission was defined as proteinuria&lt;0.5g/24h, no active urinary sediment and serum creatinine of ≤120% of baseline. Flare was defined as any abnormal proteinuria (&gt;0.5g/day) after remission. Death was treated as competing risk in survival analysis. Statistical analysis with SAS 9.4; p &lt;0.05 was considered significant. Results Out of 418 eligible patients, 209 (50%) achieved remission within the first year from LN diagnosis, 102 (24.4%) within the 2 nd and 3 rd years, 70 (16.7%) after 3 years and 37 (8.9%) never achieved remission. Sixty-six patients (15.8%) developed advanced CKD after 9.5 years on average (37 with ESKD). At baseline, these patients had a higher SLICC/Damage Index (0.6±1.2 vs. 0.3±0.7, p =0.003), lower eGFR (73±38 vs. 94±33ml/min/1.73m 2 , p &lt;0.001), higher prevalence of hypertension (85% vs. 73%, p =0.046), proliferative nephritis (combined class III and IV, 66% vs. 47.8%, p =0.017) and more often treated with ACE inhibitors or angiotensin receptor blockers (35% vs. 22%, p =0.02). The other variables did not differ significantly. Remission rates, flares and exposure to immunosuppressives after remission are shown in Table 1. Table 1. A. Time to remission, exposure to immunosuppressives and flares in all patients VARIABLE Advanced CKD (n=66 ) No advanced CKD (n=352 ) p Years from LN to complete remission 3.0 ± 3.4 1.6 ± 2.1 &lt;0.001 Years on Immunosuppressives from complete remission to outcome/last date (median) 2 (0-7) 4 (0-8) 0.008 Number of flares in first five years after LN 0 12 (18.2%) 156 (44.3%) &lt;0.001 1 14 (21.2%) 79 (22.4%) 2 or more 40 (60.6%) 117 (33.2%) B. Multivariate analysis for the outcome of advanced CKD (stage IV or worse) HR 95%CI p Serum creatinine at baseline 1.02 1.01-1.02 &lt;0.0001 Complete remission between 1-3 years (compared to remission within 1 year) 2.48 1.14-5.37 0.022 Complete remission after 3 years or no remission (compared to remission within 1 year) 2.99 1.41-6.34 0.004 Years on Immunosuppressives from complete remission to outcome/last date 0.89 0.83-0.95 &lt;0.0001 One flare (compared to no flares) 2.68 1.05-6.86 0.04 Two or more flares (compared to no flares) 3.55 1.51-8.34 0.004 Patients who achieved remission within one year from diagnosis demonstrated better outcomes compared to all other groups ( p &lt;0.0001), Figure 1. Patients with complete remission between one and three years had similar outcomes for the first 10 years from diagnosis and deteriorated during the second decade of follow-up. Figure 1. Conclusion Complete remission within the 1 st year from LN diagnosis strongly protects against advanced CKD. Flares significantly affect prognosis. One flare was associated with 2.7-fold increased risk for advanced CKD (3.6-fold for 2 or more flares). Longer time on immunosuppressives after remission is associated with decreased risk for advanced CKD. Our findings emphasize the importance of early remission as well as flare prevention with prolonged immunosuppressive use to maximize renal survival in LN. References [1]Tselios K, Gladman DD, Su J, Urowitz MB. Advanced Chronic Kidney Disease in Lupus Nephritis: Is Dialysis Inevitable? J Rheumatol 2020; 47: 1366-73 Acknowledgements The University of Toronto Lupus Clinic is supported by a grants from Lupus Ontario and Lupus Canada and donations from the Marissa and Lou Rocca, Diana and Mark Bozzo and the Stacey and Mark Krembil Families. Disclosure of Interests Konstantinos Tselios: None declared, Dafna D Gladman Consultant of: AstraZeneca, Jiandong Su: None declared, Murray B Urowitz Consultant of: GlaxoSmithKline, AstraZeneca, Merck, Bayer, UCB, Grant/research support from: GlaxoSmithKline